Skeletal diseases associated with abnormal bone formation, as exemplified by thanatophoric dysplasia (TD) and achondroplasia (ACH), are commonly called fibroblast growth factor receptor 3 (FGFR3) diseases. FGFR3 diseases are considered to be caused by gain-of-function mutations in FGFR3. FGFR3 and various molecules in the downstream signaling pathways of FGFR3 have gained attention as molecular targets for treating the diseases, and various approaches to inhibition of excessive signaling from FGFR3 have been attempted.
Several techniques for inhibiting excessive signaling from FGFR3 have previously been described, including the tyrosine kinase inhibitor reported by Jonquoy et al. (Non Patent Literature 1), the FGFR3 neutralizing antibodies reported by Rauchenberger et al. (Non Patent Literature 2), and c-type natriuretic peptide (CNP) reported by Yasoda et al. (Non Patent Literature 3). Some of these approaches successfully restored bone growth in model mice of FGFR3-related chondrodysplasia. However, the restoring effect was only confirmed in transformed cells transduced with mutant FGFR3, and the efficacy has yet to be investigated in appropriate human cell models. Also, it remains largely uncertain whether such approaches have sufficient therapeutic potential for FGFR3 diseases. These circumstances have raised demand for the development of a novel therapeutic drug.
In the field of regenerative medicine, there has been demand for techniques for converting versatile cells usable as a biomaterial into the desired cell type. Recently established are mouse or human-derived induced pluripotent stem (iPS) cells. Yamanaka et al. succeeded in establishing iPS cells by introducing the four genes, Oct3/4, Sox2, Klf4 and c-Myc, into human dermal fibroblasts (Patent Literature 1 and Non Patent Literature 4). By this technique, iPS cells can be generated from the cells of a patient to be treated and then differentiated into various types of tissue cells, and thereby can be used to reproduce the patient's clinical conditions in vitro. However, in terms of FGFR3 diseases, successful generation of iPS cells from the somatic cells of a FGFR3 disease patient has not been reported.